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Abstract

Chromosomal karyotype abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of risk of malignant transformation in individuals without apparent clinical presentation of a hematologic malignancy. To assess the association of large-scale chromosomal karyotype abnormalities and hematologic malignancy diagnosed subsequent to specimen collection, we applied the anomDetectBAF algorithm to Genome Wide Association Study data initially conducted using peripheral blood-derived DNA of 9,934 samples from the Women's Health Initiative (WHI). In this sample, large chromosomal karyotype abnormalities were observed at enrollment in 2.39% of the participants, conferring a 2.40-fold increased risk of hematologic malignancy during the median 12.62-year follow-up period (95% CI = 1.22-4.70, p-value= 0.011). Large putatively mosaic chromosomal karyotype anomalies were associated with a 3.11-fold increased risk of a hematologic malignancy in follow-up (95% CI=1.58-6.15, p-value=1.08e-3). This work suggests that large chromosomal karyotype abnormalities detected incidentally in GWAS data may provide clinically relevant risk information for subsequent hematologic malignancy diagnoses in elderly study participants.